title: Bcl-2 upregulation induced by miR-21 via a direct interaction is associated with apoptosis and chemoresistance in MIA PaCa-2 pancreatic cancer cells.
abstract: OBJECTIVE
  Bcl-2 was previously shown to be associated with apoptosis and chemoresistance and carry multiple regulating pathways. However, the roles and mechanisms of miRNA (miR)-21 in regulation of Bcl-2 in pancreatic cancer remain to be elucidated. The aim of this study was to explore the regulation of Bcl-2 expression by miR-21 and its impact on apoptosis, chemoresistance and growth of pancreatic cancer cells using a pancreatic cancer cell line, MIA PaCa-2.
  
  
  METHODS
  miR-21 mimics and inhibitor were transfected to MIA PaCa-2 pancreatic cancer cells, respectively. Alteration in Bcl-2/Bax expression was subsequently evaluated. Then, luciferase activity was observed after miR-21 mimics and pRL-TK plasmids containing wild-type and mutant 3'UTRs of Bcl-2 mRNA were co-transfected. Finally, apoptosis, chemosensitivity to gemcitabine and cell proliferation were evaluated.
  
  
  RESULTS
  Upregulation of Bcl-2 expression was detected in cells transfected with miR-21 mimics, accompanied by downregulated Bax expression, less apoptosis, lower caspase-3 activity, decreased chemosensitivity to gemcitabine and increased proliferation compared with the control cells. Cells transfected with miR-21 inhibitor revealed an opposite trend. There was a significant increase in luciferase activity in the cells transfected with the wild-type pRL-TK plasmid, in contrast to those transfected with the mutant one, indicating that miR-21 promotes Bcl-2 expression by binding directly to the 3'UTR of Bcl-2 mRNA.
  
  
  CONCLUSIONS
  Upregulation of Bcl-2 directly induced by miR-21 is associated with apoptosis, chemoresistance and proliferation of MIA PaCa-2 pancreatic cancer cells.
authors.affiliation: Department of General Surgery, Chinese Academy of Medical Sciences, Medical College Hospital, Peking Union Medical College, Beijing, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Dong
authors.forename: Yu-Pei
authors.initials: YP
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Tai-Ping
authors.initials: TP
authors.lastname: Zhang
authors.forename: Ge
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D017209:Apoptosis / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000503:physiopathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D003841:Deoxycytidine; D000093542:Gemcitabine